Sasaki K, Kushiro T, Nakagawa S, Kanmatsuse K
2nd Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Nihon Jinzo Gakkai Shi. 1999 Oct;41(7):692-6.
Although angiotensin AT1 receptor antagonist(AT1 A) improves insulin sensitivity in insulin resistant models, its effect on spontaneously hypertensive rats(SHR) has not been elucidated. We investigated the effects of AT1 A, candesartan on insulin sensitivity in SHR/Izm and the role of sympathetic activity in its mechanism. In 9-week-old SHR/Izm, candesartan(10 mg/kg/day) was given orally for 5 days. A control group received vehicle. On the 6th day, mean arterial pressure (MAP), heart rate(HR), plasma norepinephrine (PNE), plasma epinephrine(PE) and plasma dopaminc(PDA) were measured in both groups (n = 11 in each group). In the separate groups of rats, fasting blood glucose (FBG), serum sodium, serum potassium and insulin sensitivity by steady state blood glucose (SSBG) were assessed (n = 16 in the Candesartan group and n = 8 in the Control group). MAP and SSBG were significantly lower in the Candesartan group (117 +/- 2 mmHg and 138 +/- 5 mg/dl) than those in the Control group(155 +/- 6 mmHg and 164 +/- 10 mg/dl). Body weight, HR, FBG, PNE, PE, PDA, sodium and potassium were the same between the groups. In conclusion, since AT1 A, candesartal lowers blood pressure and improves insulin sensitivity irrespective of sympathetic activity in SHR/Izm, it is useful in treating hypertension associated with insulin resistance.
虽然血管紧张素AT1受体拮抗剂(AT1A)在胰岛素抵抗模型中可改善胰岛素敏感性,但其对自发性高血压大鼠(SHR)的作用尚未阐明。我们研究了AT1A(坎地沙坦)对SHR/Izm胰岛素敏感性的影响及其机制中交感神经活动的作用。在9周龄的SHR/Izm中,口服坎地沙坦(10mg/kg/天),持续5天。对照组给予赋形剂。第6天,测量两组(每组n = 11)的平均动脉压(MAP)、心率(HR)、血浆去甲肾上腺素(PNE)、血浆肾上腺素(PE)和血浆多巴胺(PDA)。在单独的大鼠组中,评估空腹血糖(FBG)、血清钠、血清钾以及通过稳态血糖(SSBG)评估的胰岛素敏感性(坎地沙坦组n = 16,对照组n = 8)。坎地沙坦组的MAP和SSBG(117±2mmHg和138±5mg/dl)显著低于对照组(155±6mmHg和164±10mg/dl)。两组之间的体重、HR、FBG、PNE、PE、PDA、钠和钾相同。总之,由于AT1A(坎地沙坦)可降低SHR/Izm的血压并改善胰岛素敏感性,且与交感神经活动无关,因此它可用于治疗与胰岛素抵抗相关的高血压。